BALTI 2: The Beta-2 Agonist Lung Injury Trial 2

Lead Research Organisation: University of Warwick
Department Name: Research Support Services

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a common and extremely serious type of respiratory failure among patients in intensive care units. Nearly half of the patients who suffer ARDS die, and many of the survivors have long-term health problems. A small-scale study suggested that intravenous salbutamol given for 7 days early in the course of ARDS may help more patients to survive. This project will determine whether this is correct, by comparing the results among over 1300 patients, half of whom (decided at random) will receive salbutamol and half of whom will receive an inactive solution.

Technical Summary

BALTI 2 is a multicentre, randomised, double-blind, placebo-controlled trial to determine whether intravenous salbutamol infusion in critically ill adult patients with acute respiratory distress syndrome (ARDS) influences 28 day mortality. The setting will be adult Intensive Care Units (ICUs) within the National Health Service in the UK with the ability to provide full (Level 3) Intensive Care.

The BALTI 2 trial is an effectiveness study, where the allocation of salbutamol or placebo infusion is determined randomly, but all other treatment decisions are left to the clinicians managing the patient. 1344 patients will be randomised within 72 hours of the onset of ARDS, and and the primary outcome is mortality 28 days after randomisation. All patients will be followed up at 1 year to determine whether salbutamol treatment has any effect on the health of survivors over the subsequent year. An economic evaluation willl be conducted alongside the trial.

Publications

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Bassford CR (2012) The rise and fall of ß-agonists in the treatment of ARDS. in Critical care (London, England)

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Howes M (2013) The Use of Beta 2-Agonists for the Treatment of Acute Respiratory Distress Syndrome in Journal of the Intensive Care Society

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Perkins GD (2014) The beta agonist lung injury trial prevention. A randomized controlled trial. in American journal of respiratory and critical care medicine

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Zheng S (2018) ResolvinD stimulates epithelial wound repair and inhibits TGF-ß-induced EMT whilst reducing fibroproliferation and collagen production. in Laboratory investigation; a journal of technical methods and pathology

 
Guideline Title The International Surviving Sepsis Campaign Guidelines for management of severe sepsis and septic shock 2012
Description Change the International Surviving Sepsis Campgain Guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Salbutamol infusion resulted in a 10.8% increase in 28-day mortality, which means that every 9 ARDS patients treated with salbutamol would result in one extra death. Consistent with 28-day mortality, there was a 8.4% increase in ICU mortality and 6% increase in hospital mortality in the salbutamol arm although this did not reach statistical significance. Again consistent with mortality data, salbutamol group had the mean 2.68 day reduction in ventilator-free days, and the mean 2.3 organ free days compared with the placebo arm. ARDS survivors in salbutamol group required average 3.4 more days in ICU than placebo arm and this nearly reached a statistical significance. We did not find a significant difference between two groups in length of ICU and hospital stay, in level 3 care bed days. The data suggested that quality of life was lower in the salbutamol group. Health economic analyses showed that costs of care were slightly higher in the salbutamol group and that salbutamol was unlikely to be cost-effective. However, our snapshot audit in 2013 showed beta-2 agonists were still used as one of drug treatments for ARDS: 8% in the UK and 14% in China patients with ARDS.
URL http://inc.sagepub.com/content/14/3/196.full.pdf
 
Description Citation in Editorial, Lancet with the publication on our trial.
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in other policy documents
Impact International practice on use of Beta-2 agonists in critically ill patients.
URL http://www.ncbi.nlm.nih.gov/pubmed/22166901
 
Guideline Title Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016
Description Our findings of Balti-2 trial provided the good evidence for revised International Guideline for Sepsis Management 2017
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact provided the scientific evidence for the guideline update.
URL http://www.survivingsepsis.org/Guidelines/Pages/default.aspx
 
Description BALTI II treatment costs subvention
Amount £178,000 (GBP)
Organisation Department of Health (DH) 
Sector Public
Country United Kingdom
Start 07/2007 
End 09/2009
 
Description The Beta Agonist Lung Injury Trial (prevention) : BALTI-prevention study
Amount £248,983 (GBP)
Funding ID PB-PG-0408-16104 
Organisation National Institute for Health Research 
Department Research for Patient Benefit
Sector Public
Country United Kingdom
Start 08/2009 
End 07/2012
 
Description a feasibility study for BALTI II
Amount £50,000 (GBP)
Organisation Intensive Care Foundation (ICF) 
Sector Private
Country Australia
Start 01/2006 
End 01/2007
 
Description IMPACT Study 
Organisation National Institute for Health Research
Department NIHR Clinical Research Network (CRN)
Country United Kingdom 
Sector Academic/University 
PI Contribution I had the original idea on evaluating IMPACT of UK critical care RCTs which was accepted by the Intensive Care Foundation and NIHR CRN for Critical Care specialty. Dr Jaimin Patel, Clinician Scientist, University of Birmingham (from my team) under my and Dr Paul Dark (Prof in University of Manchester) supervision leads this prospective national evaluation of impact of these RCTs (including Balti-2) on changes of clinical practice.
Collaborator Contribution Professor Paul Dark, Chair of the NIHR Critical Care CRN, supported the idea, contributed to the protocol and supported to obtain a CRN funding £5000 for the study,
Impact 1. to raise awareness in the UK critical care community on impact of clinical research; 2. to evaluate the outputs and outcomes of the UK Intensive Care Foundation funded clinical trials.
Start Year 2015
 
Description collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs 
Organisation NHS England
Country United Kingdom 
Sector Public 
PI Contribution Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Collaborator Contribution Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Impact Further £2,000,000 funding received.
Start Year 2018
 
Description collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs 
Organisation National Institute of Academic Anaesthesia
Country United Kingdom 
Sector Academic/University 
PI Contribution Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Collaborator Contribution Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Impact Further £2,000,000 funding received.
Start Year 2018
 
Description collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs 
Organisation Royal College of Surgeons of England
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Collaborator Contribution Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Impact Further £2,000,000 funding received.
Start Year 2018
 
Description collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs 
Organisation The Royal College of Anaesthetists
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Collaborator Contribution Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Impact Further £2,000,000 funding received.
Start Year 2018
 
Description collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs 
Organisation UK Perioperative Medicine Clinical Trials Network
Sector Academic/University 
PI Contribution Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Collaborator Contribution Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Impact Further £2,000,000 funding received.
Start Year 2018
 
Description collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs 
Organisation UK Perioperative Medicine Clinical Trials Network
Sector Academic/University 
PI Contribution Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Collaborator Contribution Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks.
Impact Further £2,000,000 funding received.
Start Year 2018
 
Description 12th Annual Critical Care Symposium, April 2015, Manchester England 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The faculties of the Symposiums are from the best researchers and the best policy makers in critical care communities, and it was great honour to be a part of it. More than 500 participants from all over the world attended this annual event for the purpose of receiving the most updated research information on use of beta-agonists in ARDS patients which sparked questions and debates.
Year(s) Of Engagement Activity 2014,2015,2016
URL http://critcaresymposium.co.uk/site3/
 
Description 14TH ANNUAL CRITICAL CARE SYMPOSIUM 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International speakers in the critical care area to demonstrate expertise to inspire further excellent research.
Year(s) Of Engagement Activity 2018
 
Description 29th and 30th Internaitonal Symposium of Intensive Care and Emegency Medicine, Brussels, Belgium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact More than thousands participants attended symposium each year to take in newly released clinical research information.
Year(s) Of Engagement Activity 2009,2010
URL http://www.ccforum.com/supplements/all
 
Description ? 16th World Congress of Anaesthesiology, Hong Kong 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Should we be using beta agonists in ARDS?
Year(s) Of Engagement Activity 2016
URL http://wca2016.com/
 
Description ? International Clinical Trial Conference July 2015, Orlando, Florida, USA 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Exchanged experience in how to handle a premature terminated clinical trial.
Year(s) Of Engagement Activity 2015
URL http://clinicaltrials.conferenceseries.com/2015
 
Description Annual Scientific Meeting on Intensive Care 2018, Kuala Lumpur, 21-23 Sept, 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Enhance our international collaborations in research and education with he final goal to improve the patients care and outcomes.
Year(s) Of Engagement Activity 2018
 
Description Intensive Care Society UK State of Art Conference 2011, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Approximately 500 participants attended the Conference to take in the BALTI-2 findings prior to the publication, which stimulated loads of questions and discussions amongst the community.
Year(s) Of Engagement Activity 2011
URL http://www.ics.ac.uk/ics-homepage/events/past-meetings/state-of-the-art-meeting-2011/
 
Description Trial of drug for acute respiratory distress syndrome stopped following increased mortality and no improvement in outcomes (BALTI-2 study)-Press Release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Intensive Care community in the world received the Release, which stimulated questions and discussions afterwards, and the Society applied the evidence into the Guideline to change ICM clinicians practice.
Year(s) Of Engagement Activity 2011
URL http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61623-1/abstract
 
Description Wessex CRN annual conference, Basingstoke, Hampshire, England, Nov 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The feedback to my presentation on our success in trial recruitment: such inspiration presentation and could we put your presentation at our CRN portal?
Year(s) Of Engagement Activity 2017
 
Description dissemination to participants 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Surviving participants informed of publication of the trial's results by post.

None yet.
Year(s) Of Engagement Activity 2011